A case report of renal cell carcinoma metastasis revealed through late‐onset thyroid nodules

Abstract Background Renal cell carcinoma (RCC) is one of the most common and prevalent cancers all around the world with a prevalence of 3%. Approximately twenty percent of patients present with metastasis at the time of diagnosis, while late metastasis in renal cell carcinoma is a quite familiar phenomenon. Head and neck and particularly thyroid metastasis from RCC are rare events. Case We present a case of a 75‐year‐old woman who developed thyroid nodules 13 years after nephrectomy for RCC. Diagnosis confirmed metastatic RCC through clinical history, histomorphology, and immunohistochemistry. Imaging studies revealed thyroid lesions without metastasis in other organs. The patient underwent total thyroidectomy and remains symptom‐free after 2 years of follow‐up. Conclusion This case highlights the importance of considering metastatic lesions is crucial in managing thyroid nodules in patients with a history of cancer, particularly RCC.


| INTRODUCTION
Renal cell carcinoma (RCC) is the predominant form of kidney neoplasms and accounts for approximately 3% of all malignant tumors in humans. 1 Survival is highly dependent on the stage of disease at diagnosis, with a 5-year survival of 93% for stage 1, 72.5% for stage 2 and 3 regional disease, and only 12% for stage 4. 2 Risk stratification in RCC plays a crucial role in determining prognosis, treatment decisions, and follow-up strategies.Several established risk stratification systems are commonly used in clinical practice.Tailored follow-up regimens are crucial in the management of high-risk RCC, considering the potential for disease recurrence and the emergence of new insights regarding adjuvant therapies.immune checkpoint inhibitors, such as nivolumab and pembrolizumab, have also shown promising results in the adjuvant setting for high-risk RCC.
These agents enhance the immune response against cancer cells and have the potential to improve outcomes in this patient population. 3ughly around 30%-50% of patients have metastasis at the time of diagnosis.Although metastasis to bone, brain, and lungs is common in RCC, it may spring up in unusual sites such as skin, testis, and maxillary. 2,4Most recurrences, approximately 78%, occur within the first five years following nephrectomy.However, late metastasis, defined as distant recurrence occurring more than 10 years after nephrectomy, is not an uncommon occurrence in patients with renal cell carcinoma. 5The most common sites for metastatic RCC are the lungs, lymph nodes, bone, and liver.The precise mechanism of RCC metastasis is still unknown; however, hematogenous metastasis, lymphogenous dissemination, and direct invasion are some possible ways. 6,7tastasectomy is typically reserved for cases where complete resection is feasible unless the primary goal of treatment is palliative symptom management.When considering surgery, it is crucial to weigh the potential morbidity and mortality associated with metastasectomy. 8,9 addition to surgery, targeted therapies such as tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have emerged as notable alternatives for treating metastatic renal cell carcinoma (RCC).These systemic therapies have demonstrated impressive effectiveness in controlling tumor growth and improving survival rates in patients with metastatic disease.Furthermore, there are less invasive treatment options available for metastatic RCC patients.Procedures like radiofrequency ablation (RFA), stereotactic ablative radiotherapy (SABR), and cryoablation (CA) offer alternative approaches that are less invasive compared to surgical interventions.
These techniques can be utilized to destroy or ablate tumors while minimizing the impact on surrounding healthy tissues.When determining the most suitable treatment approach, it is crucial to consider various factors such as the feasibility of complete resection, the potential for palliative symptom relief, morbidity and mortality associated with surgery, and the effectiveness of targeted therapies or alternative interventions.A comprehensive evaluation by a multidisciplinary team is essential to ensure that patients receive the most appropriate and effective treatment for their metastatic RCC. 9 Even though the thyroid gland has an abundant blood supply, metastatic thyroid cancer is rare, 1.15%-3%.Faster blood flow, high oxygen saturation, and high iodine content of the thyroid gland are proposed as the impeding factors for the growth of metastasis.
Metastasis to the thyroid is not uncommon in biopsy; the incidence is 1.2%-24%.[12] The uniqueness of this case lies in the rare occurrence of RCC metastasis to the thyroid gland, the significant time interval between the initial nephrectomy and the detection of metastasis, and the successful management through total thyroidectomy.These findings contribute to the medical literature on the behavior and clinical presentation of renal cell carcinoma and highlight the importance of considering metastasis to the head and neck region in patients with a history of RCC.A fine needle aspiration (FNA) procedure was conducted to investigate the left thyroid lobe nodule further.The aspirated nodule yielded highly cellular smears, which displayed three-dimensional clusters, papillae, and sheets of neoplastic cells.These cells exhibited round and ovoid hyperchromatic nuclei, conspicuous nucleoli, and abundant clear and finely granular cytoplasm.The background of the smears appeared bloody.(Figure 1).

| CASE
An immunohistochemistry (IHC) study on cell block was performed.Tumoral cells showed positive staining for CD10, PAX8 and CA-IX and they were negative for TTF1 (Figure 2).The patient has been regularly followed up for 2 years, and there have been no complaints or signs of recurrence or metastasis.

| DISCUSSION
The findings of this case study contribute to the existing literature by highlighting the rare occurrence of late metastasis to the thyroid gland to metastasize to the thyroid gland, usually involving concurrent metastatic involvement of other organs.However, isolated thyroid metastasis is infrequent. 13e case report emphasizes the importance of utilizing ultrasound imaging, fine needle aspiration with immunohistochemical staining, and PET scans for accurate diagnosis and evaluation of metastatic lesions.In this particular case, no evidence of metastasis was detected in other areas of the body, and a successful total thyroidectomy was performed without complications.
Sonographically, metastatic RCC to the thyroid gland is characterized by solid or solid cystic, irregularly shaped nodules with heterogeneous echogenicity, with or without calcification. 14Although ultrasound imaging alone may not provide definitive discrimination, fine needle aspiration with immunohistochemical (IHC) staining can help differentiate primary thyroid carcinoma from metastatic thyroid lesions, particularly in patients with a known history of malignancy.F I G U R E 3 A PET/CT scan of a patient revealing a fused pathological uptake in the thyroid gland, suggesting metastatic involvement in a patient diagnosed with renal cell carcinoma.
Additionally, PET scans are considered beneficial complementary tools for evaluating distant metastasis and guiding treatment planning. 15nal cell carcinoma is known for synchronous and metachronous metastasis. 16About 30% of patients with localized RCC experience recurrence after surgery, with the majority occurring within 5 years of resection. 17However, 4%-11% of RCC patients may experience relapse even after 10 years. 18,20Our patient encountered this complication 13 years after the initial successful therapy.Late metastasis cases, including those with disease-free survival exceeding 10 years, have been reported. 19,20e concept of temporary mitotic arrest or cellular dormancy may partially explain the occurrence of overt metastasis or recurrence many years after successful treatment of the primary tumor.[22] Metastasis to the head and neck, particularly the thyroid gland, is uncommon.However, recent studies have revealed that approximately 1.9%-22.4% of patients with disseminated metastasis have thyroid gland metastasis based on autopsy results. 10,11On the other hand, thyroid nodules are a common problem in adults, and their incidence increases with age.However, less than 5% of these nodules are malignant. 23,24It has been proposed that the thyroid gland's high vascularity and iodine content are significant factors impeding tumor implantation.However, any structural deformity in the thyroid gland may increase the chance of tumor seeding. 13,24| CONCLUSION This case highlights the importance of considering metastatic RCC in the diagnosis of thyroid nodules, especially in patients with a history of RCC.Ultrasonography, fine needle aspiration with immunohistochemistry, and PET scans aid in diagnosing and evaluating metastatic lesions.The presence of thyroid nodules in a patient with a history of RCC requires a change in approach for evaluating and managing the nodules.Ultrasound alone may not discriminate between primary thyroid carcinoma and metastatic lesions.Therefore, FNA with immunohistochemical staining aids differentiation in patients with a known history of malignancy.Further research is needed to understand the mechanisms of late metastasis and factors contributing to tumor seeding in the thyroid gland.In summary, a comprehensive approach involving FNA with immunohistochemical staining, ultrasound, PET scans, and consideration of metastatic lesions is crucial in managing thyroid nodules in patients with a history of cancer, particularly RCC.
The 75-year-old female patient presented to her endocrinologist at Namazi Hospital with a complaint of a neck mass in April 2021.She denied experiencing any difficulty in breathing (dyspnea), changes in voice (hoarseness), or difficulty swallowing (dysphagia).Thirteen years ago, the individual underwent a radical nephrectomy to treat a tumor in their right kidney.A histopathological study of the surgically removed tissue confirmed that the tumor was clear cell renal cell carcinoma (pT1a N0 M0).The patient has been undergoing annual follow-up with abdominal CT and chest X-ray for 5 years following radical nephrectomy, along with annual history and physical examinations up to the present time.During the physical examination, multiple nodules were identified in both thyroid gland lobes.The results of the thyroid function test showed a thyroid-stimulating hormone (TSH) level of 1.08 mIU/L (normal range: 0.4-4.0mIU/L), a free thyroxine (FT4) level of 1.6 ng/ dL (normal range: 0.7-1.8ng/dL), and a free triiodothyronine (FT3) level of 2.2 pg/mL (reference range: 2.3-4.2pg/mL).An ultrasonographic examination was performed, revealing the presence of multiple nodules in both lobes.The largest nodule, measuring 22 Â 21 mm, was found in the left lobe and appeared hypoechoic and solid.Another smaller nodule with an irregular border and peripheral calcification was observed in the right lobe.
Consequently, based on the patient's clinical history, histomorphology, and immunohistochemistry (IHC) findings (Figure2), a diagnosis of metastatic renal cell carcinoma (RCC) was established.To assess the potential presence of metastasis in other organs, a fluorodeoxyglucose (FDG) PET-CT scan was conducted.The scan revealed a low attenuation lesion in the lower aspect of the left thyroid lobe, indicating FDG uptake, and another non-FDG-avid low attenuation lesion in the right thyroid lobe, which contained an eccentric calcified focus (Figure3).No evidence of metastasis was detected in other areas of the body.In light of these findings, a successful total thyroidectomy was performed without any complications during or after the operation.Based on the histopathology report, the examination of the thyroid sample revealed a neoplastic nodule measuring 23 Â 22 mm in the left lobe.The nodule consisted of large clear cells.Immunohistochemical staining demonstrated that the tumor cells were positive for vimentin, CD10, PAX8, and CA-IX.However, they tested negative for thyroglobulin, thyroid transcription factor-1 (TTF-1), and chromogranin.These findings confirmed the renal origin of the tumor, indicating clear cell carcinoma.
Fine needle aspiration biopsy of a thyroid nodule.(A, B) Papillary clusters and three-dimensional arrangements of abnormal cells observed (Papanicolaou stain; magnification, Â100 and Â200; scale bar, 100 and 50 μm).(C) Presence of a fibrovascular core and vacuolated cytoplasm with clear appearance (Wright-Giemsa stain; magnification, Â200; scale bar, 50 μm).(D) Cellblock analysis reveals distinct well-defined cells with clear cytoplasm (H&E stain; magnification, Â200 and Â400; scale bar, 50 and 20 μm).No colloid material is detected in the smears or cell block.fromrenal cell carcinoma (RCC) many years after nephrectomy.Isolated thyroid metastasis is uncommon, and the diagnosis was conmetastasis to the thyroid gland is relatively rare, RCC is among the most frequently reported malignancies